Apparatus, systems and methods for processing and treating a biological fluid with light

ABSTRACT

Apparatus ( 10 ), systems and methods are disclosed for treating a biological fluid with light. A container ( 206 ) of biological fluid is introduced into a fluid treatment chamber ( 40 ) where it is contacted with light provided by one or more light sources ( 60, 70 ) in proximity to the fluid treatment chamber ( 40 ). A light sensing system ( 650 ) senses the intensity of illumination of the light. A radiometer ( 460 ) may be inserted into fluid treatment chamber ( 40 ) to calibrate the light sensing system ( 650 ). An electronic control system ( 600 ) utilizes an interface circuit board ( 606 ) to interface a computer circuit board ( 602 ) to a display panel ( 37 ), a user interface panel ( 39, 39   a ), a relay circuit board ( 640 ), light sensors 404 and various other sensors ( 649 ). A detector ( 385 ) senses agitating movement of a tray ( 90 ) that contains biological fluids. Methods include calibrating ( 781 - 785 ), sensing ( 770 - 773 ) and correcting ( 774 - 775 ) light intensity measurements, and determining the length of treatment ( 776 ) to reach a desired illumination dose. A radiometer ( 460 ) is equipped with a plurality of light sensors ( 469 ) disposed on both sides to measure light intensity in chamber ( 40 ) and to provide a reference for calibrating light sensing system ( 650 ).

CROSS-REFERENCE TO RELATED APPLICATION

This is a divisional patent application of co-pending patent applicationSer. No. 10/269,409, filed on Oct. 11, 2002, which is acontinuation-in-part of U.S. application Ser. No. 09/325,325, filed Jun.3, 1999, now U.S. Pat. No. 6,565,802 B1.

BACKGROUND OF THE INVENTION

The present invention generally relates to apparatus, systems andmethods for processing and treating biological fluids, such as blood andblood components. More particularly, the present invention relates tosuch apparatus, systems and methods having a light sensing system tomeasure the illumination intensity of a plurality of lamps, a radiometerwith a plurality of light sensors that may be inserted into theapparatus to calibrate the light sensing system, an interface printedcircuit board that interfaces a computer printed circuit board with theelectronics and sensors of the apparatus, a sensor arrangement to detectthe motion of an agitator for agitating the biological fluid, methodsfor calibrating, sensing and correcting light intensity measurements, aradiometer for accurately measuring light in the apparatus to provide areference for calibrating the light sensing system, and methods fordetermining the length of treatment to reach a desired illumination doseby using the calibrated light sensing system.

Apparatus, methods and systems for treating biological fluids, such asblood and blood components, with light are well known. For example, U.S.Pat. No. 4,952,812, incorporated by reference herein, discloses anapparatus for treating unwanted white blood cells in plateletconcentrate with ultraviolet radiation to limit the ability of whitecells to trigger an immune reaction in a patient. To treat containers ofplatelet concentrate, the containers are placed on a slidable drawerthat is introduced into a housing between facing arrays of lamps forirradiation from both sides of the container. During irradiation, thedrawer (or a portion of the drawer) may be pivoted in a rocking motionto agitate the platelet concentrate.

U.S. Pat. No. 5,557,098, also incorporated by reference herein,discloses a system and apparatus for treating a biological fluid withlight for the purpose of inactivating pathogens that may be present inthe biological fluid. A slidable drawer is used to position thecontainers of biological fluid between facing arrays of light emittingdiodes. Extended flaps on the containers, located outside the lightfield, are automatically punched to indicate different stages of thelight treatment.

U.S. Pat. No. 6,245,570, which is also incorporated by reference herein,discloses apparatus and methods for treating a container of a bloodproduct between two facing arrays of light. The container includes alight sensitive tape that changes color when exposed to ultravioletlight, thereby indicating when the treatment process is complete.

Still other apparatus and systems for treating biological fluid aredisclosed in U.S. Pat. No. 4,726,949, U.S. Pat. No. 5,709,991, U.S. Pat.No. 6,433,343 and U.S. Pat. No. 6,190,609, all of which are incorporatedby reference herein.

Prior art radiometers typically measure light intensity at a singlepoint and from only one direction.

While the prior art apparatus, systems and methods have generally workedsatisfactorily, there is a need for improved apparatus, systems andmethods that provide, for example, improved reliability and accuracy,greater flexibility and efficiency, improved ease of use andserviceability, as well as enhanced tracking, record keeping and thelike.

SUMMARY OF THE INVENTION

The following summary is intended as an overview of certain aspects ofthe present invention. It is not intended by this summary to limit orexpand the scope of the claims, which define the scope of the presentinvention. The mention of certain features or elements in this summarydoes not mean that such elements or features are necessary to the use orpractice of the invention in its broader or other aspects, or that suchshould be read into claims that do not expressly recite such feature orelement. Conversely, the absence of any mention of certain elements orfeatures is not intended to detract from the significance of suchelements or features in those claims in which they are expresslyincluded.

In one aspect, the present invention is embodied in an apparatus fortreating a biological fluid in a fluid treatment chamber having aplurality of lamps and a light sensing system to determine the lightintensity emitted from the plurality of lamps with the light intensitymeasurements corrected with previously determined calibrationcoefficients to provide a calibrated light intensity.

In another aspect, the present invention is embodied in a light sensingsystem for apparatus to treat a biological fluid in a fluid treatmentchamber with at least one light source. The system includes at least onelight sensor to sense the light level within the treatment chamber. Thelight sensor preferably provides an output frequency signal that isrelated to the sensed light intensity. This frequency signal is countedand analyzed to determine the light intensity in the treatment chamber.Multiple frequency signals from multiple sensors may be multiplexedprior to counting. The count of the frequency signals may be correctedwith calibration coefficients that were determined in a priorcalibration procedure.

In another aspect, the present invention is also embodied in anelectronic control system for the biological fluid treatment apparatuswith a computer circuit board and an interface circuit board tointerface a display, an operator input device, the light sensing system,the lamp control system and a plurality of sensors and the like with thecomputer circuit board.

The present invention is also directed to methods for calibrating,sensing and correcting light intensity measurements. The methods alsoinclude determining the length of treatment of a biological fluid inorder to reach a desired illumination dose.

In yet another aspect, the present invention is embodied in a radiometerwith a plurality of light sensors disposed on at least one side, andpreferably on opposite sides of the radiometer, to measure lightintensity from at least one array of illumination sources. Theradiometer is separately calibrated to provide accurate lightmeasurements over a predetermined area of the treatment chamber, whichmeasurements are used by a central processing unit of the apparatus todetermine appropriate calibration coefficients for the light sensingsystem. Preferably, the radiometer simulates the dimensions and geometryof the product to be treated with light in the apparatus.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a perspective view of an apparatus for treating a biologicalfluid with light, embodying the present invention;

FIG. 2 is a perspective view of the apparatus of FIG. 1 showing themodular components of the apparatus separated;

FIG. 3 is a perspective view of the apparatus of FIG. 1 with the frontaccess door open;

FIG. 4 is a perspective view of the apparatus of FIG. 1 with front, topand side panels removed;

FIG. 5 is a partially exploded view of the apparatus of FIG. 1;

FIG. 6 is a perspective view of a light drawer with a socket panel open;

FIG. 6A is an exploded view of the light drawer of FIG. 6.

FIG. 7 is a perspective view of a fluid container carrying tray;

FIG. 8 is a perspective view of the fluid carrying drawer with trayremoved;

FIG. 8A is a partial side view of the drawer tilt knob and assembly ofthe fluid carrying drawer;

FIG. 8B is a modified partial side view of the drawer tilt knob andassembly of the fluid carrying drawer;

FIG. 9 is another perspective view, from the underside, of the fluidcarrying drawer without the fluid container carrying tray;

FIG. 10 is a front view of the fluid carrying drawer with fluid carryingtray removed showing side-to-side oscillation of the tray;

FIG. 11 is a perspective view of a container marker assembly;

FIG. 11A is another perspective view, from the underside, of thecontainer marker assembly;

FIG. 12 is an enlarged perspective view of an individual marking unit ofthe container marker assembly;

FIG. 13 is a perspective view of stacked apparatus embodying the presentinvention;

FIG. 14 is a block diagram of one embodiment of a control system for theapparatus of the present invention;

FIG. 14A is a perspective view of a light sensing device which may beused with the apparatus of FIG. 1;

FIG. 15 is a plan view of a disposable fluid processing set embodyingthe present invention;

FIG. 16 is a plan view of another disposable fluid processing setembodying the present invention;

FIG. 17 is a plan view of a disposable fluid processing set embodyingthe present invention in position for attachment with containers of acollected biological fluid;

FIG. 18 is a perspective view of a part of the disposable fluidprocessing set embodying the present invention that includes at leastone container disposed within a holder;

FIG. 18A is a perspective view of an alternative embodiment of theholder in a closed position with containers disposed therein;

FIG. 18B is a perspective view of the holder of FIG. 18A in an openposition but without container(s);

FIG. 18C is a perspective view of another alternative embodiment of aholder in an open position;

FIG. 18D is a perspective view of another alternative embodiment of aholder with the frame portions separated;

FIG. 19 is a flow chart showing the start-up phase of the control systemfor the present invention;

FIG. 20A is a flow chart showing the pretreatment phase of the controlsystem for the present invention;

FIG. 20B is a continuation of the flow chart of FIG. 20A;

FIG. 21 is a flow chart showing the treatment phase of the controlsystem for the present invention;

FIG. 21A is a flow chart showing the steps employed to measure theillumination intensity during the treatment phase of the apparatus ofthe present invention;

FIG. 21B is a flow chart showing the steps employed in calibrating theapparatus of the present invention to measure the illumination intensityin accordance with the present invention;

FIG. 22 is a flow chart showing the operator initiated instrumentsettings functions of the control system for the present invention;

FIG. 23 is a flow chart showing the diagnostic functions of the controlsystem for the present invention;

FIG. 24 is a rear perspective view of one embodiment of thefluid-carrying drawer, fluid container carrying tray and an alternativeembodiment of the agitation assembly;

FIG. 25 is a top view of the motor for moving the fluid-carrying drawer;

FIG. 26 is an exploded view of the drawer sub-assembly andfluid-carrying tray;

FIG. 27 is a perspective view of the fluid carrying drawer with thefluid carrying tray placed therein;

FIG. 28 is a perspective view from the underside, of the fluid carryingdrawer without the fluid carrying tray;

FIG. 29 is a perspective view of an radiometer embodying the presentinvention;

FIG. 30 is a cross-sectional view, taken along section line 30-30 of theradiometer shown in FIG. 29;

FIG. 31 is an exploded view of the radiometer of FIG. 29;

FIG. 32 is a perspective view of the radiometer positioned within acompartment of the fluid container carrying tray;

FIG. 33 is a block diagram showing the preferred interconnections andrelationships between the printed circuit boards that contain theelectronic circuitry for the control system of the present invention;

FIG. 34 is a diagram of the lamps and the light sensing circuitry forthe light sensing system of the present invention; and

FIG. 35 is an electrical schematic diagram of the light sensingcircuitry.

DETAILED DESCRIPTION

For purposes of illustration, the various aspects of the presentinvention will be described, in large part, in connection with theirpreferred embodiments. However, it should be recognized that theapparatus, systems and methods embodying the different aspects of thepresent invention are not limited to the specific details describedherein.

An apparatus for treating a biological fluid is generally shown in FIGS.1-14 and is referred to herein generally as light box 10. Light box 10may be used for treating a variety of materials for a variety ofpurposes.

Light box 10 is particularly useful in the treatment of biologicalfluids. As used herein, biological fluid refers to any fluid that isfound in or that may be introduced into the body including, but notlimited to, blood and blood products. As used herein “blood product”0refers to whole blood or a component of whole blood such as red bloodcells, white blood cells, platelets, plasma or a combination of one ormore of such components that have been separated from whole blood.

One specific, non-limiting use of light box 10 is in the treatment of ablood product that has been combined with a photochemical agent foractivation when subjected to light. Such photochemical agents are used,for example, in the inactivation of viruses, bacteria, white blood cellsand other contaminants (collectively referred to herein as “pathogens”).In pathogen inactivation applications, the activated agent inactivatespathogens that may be present in a blood product.

Typically, the biological fluid to be treated is introduced into a fluidtreatment chamber within light box 10 in flexible, plastic,sterilizable, translucent, biologically compatible containers. Inaccordance with aspects of the present invention, the containers may beintegrally connected to other containers and plastic tubing useful inthe processing of the biological fluid both before and after thetreatment provided by light box 10. Examples of the disposableprocessing set and its components are shown in FIGS. 15-18. The lightbox, the disposable processing set and the methods of using them aredescribed in more detail below.

a. Light Box

As shown in FIG. 1, light box 10 includes a housing 12 defined by toppanel 14, bottom panel 16, front and rear panels 17, and side panels 18.Housing 12 is supported by feet 13 attached to bottom panel 16 (FIG. 4).In a preferred embodiment, feet 13 are rubber or other elastomericmounts. Side panels 18 may include handles 22 for grasping andtransporting light box 10. An openable or removable door 24 in sidepanel 18 allows for access to the interior of light box 10 and, morespecifically, the electronic components of light box 10, which aredescribed in more detail below. Door 24 may be opened or removed byturning fasteners 25.

For convenience and efficiency, it is preferred that light box 10 befairly compact. In one, non-limiting example, light box 10 may beapproximately 100-120 cm wide, 20-100 cm deep and between approximately30-40 cm high. A compact instrument allows, for example, for placementof a greater number of instruments per treatment center and/or may allowtwo or more instruments to be stacked on top of each other (as shown inFIG. 13), resulting in greater throughput of biological fluid perhorizontal area or space (i.e. bench space, shelf space or the like).

Light box 10 may include a control module 26 and a fluid treatmentmodule 28. As described in more detail below, control module 26 mayinclude and/or house the command and control elements for the treatmentof biological fluid. Fluid treatment module 28 houses the elements andcomponents where fluid processing takes place.

Control module 26 and fluid treatment module 28 may be contained in thesame housing but in a preferred embodiment, as shown in FIG. 2, they arereadily separable modules. Control module 26 and fluid treatment module28 are electrically and physically connected when light box 10 is inuse, but may be separated as shown in FIG. 2. In one embodiment, controlmodule 26 and fluid treatment module 28 are held together, in part, by adraw pin 30 (FIG. 4), which holds together interfitting parts of themodules. Alternatively, modules 26 and 28 may be held together bycaptive fasteners 31 (also shown in FIG. 4) with or without draw pin 30.Control module 26 and fluid treatment module 28 may be separated byremoving draw pin 30 and/or turning of fasteners 31 shown in FIG. 4.Fasteners 31 may be accessed by removing door 24 (shown in FIG. 1) inside panel 18. Of course, other means of connecting and readilyseparating control and fluid treatment modules may be used, including,mating clips and slots on the facing panels of the control 26 and fluidtreatment module 28.

Providing light box 10 in two readily separable modules 26 and 28 allowsfor easier access to the control and fluid treatment modules 26 and 28and, generally, provides for easier serviceability of light box 10. Forexample, if off-site service is required for control module 26 only,that module can be removed without requiring removal and transport ofthe entire light box 10.

As shown in FIGS. 1 and 2, the exterior of control module 26 includes acontrol panel 32 located in the front of light box 10. Control panel 32includes, a display screen 37 such as, but not limited to, an LCDdisplay for providing graphical, textual and alphanumerical informationto the operator regarding the treatment process. Also included withincontrol panel 32 of control module 26 is a key pad 39 to allow operatorcontrol over the process and/or for data entry by the operator. Adifferent keypad 39 a is shown in FIG. 29, which is a four-by-fourmatrix with 10 numerical digits including the * and # functions, such asthe keypads typically provided on telephones. Additional means of dataentry are provided by bar code reader scanner 41 which, when not in use,rests in slot 43 or a scanner holder. A trough 45 may be provided forthe coiled cable of bar code reader 41. Alternatively, coiled cable ofbar code reader/scanner 41 may be routed through the rear of scannerholder 43. Control panel may also include the on/off switch 35 for lightbox 10.

The interior components of control module 26 are generally shown in FIG.4. Control module 26 will typically include a programmablemicroprocessor for operation of light box 10 including centralprocessing unit 27 and memory devices such as random access memory (RAM)and EPROMS for the system program storage and non-volatile memory forback-up data storage. Control module 26 may further include an isolationtransformer 29 for converting an AC input voltage to a DC control systemvoltage and for maintaining leakage current within acceptable limits formedical devices. Other components within control module 26 may includepower supply 167, input/output board 33 and a power inlet module 34,filtered pass through 34 b for use with an external light intensitysensing device and filtered output pass through 34 a.

Control module 26 may be adapted for connection to external componentssuch as a printer 500 (FIG. 14) through parallel and/or serial ports612, 613 and/or 616 (FIG. 33) (such as to a label printer through aserial port), or to a computer printed circuit board (PCB) 602 or, forexample, to an Ethernet port 621. Computer PCB 602 can receive data fromthe several instruments, allowing the operator at a treatment center toretrieve information regarding the several procedures. As will beappreciated by one of ordinary skill, control module 26 may also includeother components such as additional printed circuit boards shown in FIG.33. While FIG. 14 illustrates one embodiment of an electronic controlsystem to light box 10, the preferred embodiment is illustrated in FIGS.33-35, which are discussed in detail below.

Turning now to the fluid treatment module 28, as shown in FIGS. 1-3,fluid treatment module 28 includes front door 36 which when opened,allows for introduction and removal of the biological fluid into a fluidtreatment chamber, as described in more detail below. The front panel 17of fluid treatment module 28 may also be opened to allow for fulleraccess to the interior of fluid treatment module. As shown in FIG. 3,panel 17 may include fasteners 17 a and ball detents which, when turned,allow front panel 17 to be opened or removed.

FIGS. 4 and 5 generally show the interior of fluid treatment module 28with at least top panel 14 and front panel 17 removed. As best seen inFIG. 5, fluid treatment module 28 includes an interior framework 38 thatdefines, in part, a fluid treatment chamber 40 and light chambers 42 and44 for housing light sources (described in more detail below). Theframework 38 may typically be constructed of any sturdy material whichwill allow light box 10 to support one or more additional light boxes asgenerally shown in FIG. 13. A preferred material is aluminum and, inparticular, Aluminum 6061 hardened to T-6 or Aluminum 5052/H32.

Returning to FIG. 5, the light chambers 42 and 44 are located above andbelow fluid treatment chamber 40 to provide two-sided illumination ofthe biological fluid. Of course, it will be appreciated that light box10 may include a single light chamber, placed in close proximity tofluid treatment chamber or two or more light chambers disposed around afluid treatment chamber in other than “top and bottom” positions.

As shown in FIGS. 3 through 5, fluid treatment chamber 40 is adapted toreceive fluid carrying drawer 50. Light chambers 42 and 44 are adaptedto receive light drawers 60 and 70. Fluid treatment module 28 may,optionally, further include a container marker assembly 74 shown, forexample, in FIG. 5. Marker assembly 74 may carry one or more markers 76a-76 d for marking containers, before and/or after treatment, as will bediscussed in more detail below.

Turning more specifically to a description of fluid carrying drawer 50,as shown in FIG. 13, fluid carrying drawer 50 allows for introduction ofbiological fluid into fluid treatment chamber 40. Fluid carrying drawer50 may be moveable, either manually or automatically, into and out offluid treatment chamber 40. Where manual movement of fluid carryingdrawer 50 is required, drawer 40 may include handle 80. In oneembodiment, movement of fluid carrying drawer 50 is facilitated byslides 82 on either or both sides of drawer 50, which are disposedwithin rails 86 of framework 38, as best seen in FIGS. 8, 9 and 13.Alternatively, fluid carrying drawer 50 may include rollers or otherdevices that allow for movement of drawer 50 into and out of fluidtreatment chamber 40.

For ease of loading and unloading containers of biological fluid, fluidcarrying drawer 50 preferably includes a pivot mount that permits thedrawer to be tilted downwardly when fully withdrawn. The ability to tiltdrawer 50 downwardly may be particularly useful for loading containersof fluid in the upper light boxes where two or more light boxes arestacked on top of each other, as shown in FIG. 13. In one embodiment,fluid carrying drawer 50 may be hingedly attached to framework 38 sothat when fluid carrying drawer 50 is fully opened and is outside ofhousing 12, front edge of drawer 50 may be tilted downwardly at, forexample, a 20-45° angle, and preferably a 30° angle.

To allow tilting of fluid carrying drawer, light box 10 may includespring loaded tilt knob 83 which, when pulled, releases fluid carryingdrawer 50 and allows it to be tilted in the manner described above. Morespecifically, as shown in FIG. 8A, tilt knob 83 is connected to rod 82 awhich is attached to slide 82 (FIG. 9). The end of rod 82 a is coupledto pivot member 83 a, which is connected to ring 83 b attached to drawer50. Rod 82 a further includes a spring 82 c and spring stops 82 d. Whenthe end of rod 82 a is coupled to pivot member 83 a, movement of ring 83b is prevented (as shown in FIG. 8A). However, when knob 83 is pulled,(as shown in FIG. 8B) rod 82 a is uncoupled from pivot member 83 a,allowing ring to rotate relative to pivot member 83 a and, thereby,allowing drawer 50 to be tilted downwardly, as shown in FIG. 13.

Alternatively, light box 10 and more specifically, fluid-carrying drawer50, may include release button 300 which, when pressed, allows drawer 50to be downwardly tilted in the manner shown in FIGS. 26-28. As shown inFIGS. 27-28, button 300 actuates rod 302, which is attached to bellcrank 304. As rod 302 is moved forward, bell crank 304 pivots aroundcylinder 306. The pivoting of bell crank 304 pulls rod 308, therebydisengaging latch pawl 310 from its fixed position on the internalframework of light box 10 (not shown). With latch pawl 310 disengaged,fluid-carrying drawer 50 may be tilted downwardly for ease of loading ofthe biological fluid containers as generally shown in FIG. 13.

Returning to FIGS. 8-9, fluid carrying drawer 50 is generally open andincludes a central cavity 88 to allow for placement of acontainer-carrying tray 90 shown in FIG. 7. Container carrying tray 90may be integral with fluid carrying drawer 50, although, a removablenon-integrated tray 90 may be preferable for easier container loadingand/or tray cleaning.

During treatment of the biological fluid, it may be desirable that thefluid within fluid carrying drawer 50 be continuously or periodicallyagitated to provide mixing of the biological fluid and ensure thatsubstantially all of the biological fluid is sufficiently and uniformlyexposed to light and/or any photochemical agent. Accordingly, fluidcarrying drawer 50 may be attached to means for agitating the biologicalfluid.

As shown in FIGS. 9 and 10, fluid carrying drawer 50 may include anagitation assembly that, for example, provides side-to side oscillationof tray 90. Agitation assembly may include a pair of fixed lower rails95 b that extend front to back within light chamber. Upper rails 95 aare attached to the lower rails by pivotally attached link arms 93 a and93 b. The link arms allow side-to-side motion of the upper rails 95 a.To provide oscillation, an electrical motor 92 is attached to lower rail95 b. Motor 92 rotates a cam 97 a. Cam 97 a may be an L-shaped crank orbracket attached to roller 97. Roller 97 is captured between parallelwalls 97 b depending from upper rail 95 a. As crank 97 a causes roller97 to orbit around the motor 92 axis, roller slides fore and aft and upand down between walls 97 b, imparting side-to-side motion of upper rail95 a.

Alternatively, as shown in FIG. 24, the agitation assembly may includeI-shaped legs 320. As shown in FIG. 24, the bottom flared portions oflegs 320 are affixed to lower rods 322 which are, in turn, affixed tothe floor of the fluid treatment module 26. The top flared portions oflegs 320 are fixed to plate 324, which receives fluid-carrying drawer 50(and tray 90), as shown in FIG. 24.

Yoke 326 is fixed to and depends from one side of plate 324. Yoke 326includes a gap 328 that receives roller 330 of motor 334. As shown inFIG. 25, motor 334 includes a central shaft 336, which receives a cam338. Cam 338 may be an L-shaped crank or bracket. Shaft 340 of cam 338receives roller 330. As shown in FIG. 25, roller 330 is offset fromshaft 336 by a predetermined distance.

As will be appreciated by those of skill in the art, rotation of cam 338causes an eccentric motion and movement of roller 330. Specifically,roller 330 slides fore and aft and up and down and moves yoke 326accordingly, resulting in side-to-side movement of fluid-carrying tray90.

In one embodiment, roller 330 is offset from shaft 336 by a distance ofanywhere between 0.5 and 1 inch and, more preferably, 0.75 inches. Thisresults in a total displacement of fluid-carrying tray 90 ofapproximately 1.5 inches.

Light box 10 may include one or more light sources, preferably disposedabove and below fluid treatment chamber 50. For ease of serviceability,such as lamp replacement, it is preferable that the light source(s) bereadily accessible. As used herein, “readily accessible“ means thataccess to the light source can be quickly and easily had without the useof, for example, a screwdriver or other tools. For example, in oneembodiment, it may be desirable that the light source be eitherpartially or completely removable from the housing 12 and/or fluidtreatment module 28. The light source(s) may be accessible through anyone of the front, side, top or bottom panels. In one embodiment, thelight sources are housed in light drawers 60 and 70. As shown in FIG. 5,when front panel 17 and/or door 36 are removed or opened, light drawersmay be moveable (or even completely removable) into and out of fluidtreatment module 28. Light drawers 60 and 70 may include slides 99 (FIG.6) attached to the bottom surface of drawers 60 and 70. Slides 99 restand move on brackets 96 and slide mounting blocks 98 of framework 38 asshown in FIG. 5. Light drawers 60 and 70 may also include handles 84 forgrasping during insertion and removal.

As shown in FIGS. 6, light drawer 60 and/or 70 may be divided into twoor more chambers 101 and 103 separated by dividing wall 102. Dividingwall 102 minimizes light from one light chamber of radiating into theother light chamber. This ensures that the light emitted from each lampor lamp array and contacting the biological fluid is substantiallyconstant. In addition, each of the lamp arrays within light chambers 101and 103 may be independently monitored and controlled from controlmodule 26. Thus, when one array of lamps is turned off, the other arrayof lamps may remain on. As described in more detail below, this may beparticularly useful where two or more containers of biological fluidrequiring different levels of treatment are being treated.

Each of light chambers 101 and 103 of light drawer 60 or 70 is generallydefined by four sidewalls 105 a-d and a bottom wall 107. Walls 105 a-dand 107 may be made of or coated with a reflective material to maximizethe amount of light delivered to the biological fluid. In one specificembodiment, where the light source provides light in the ultraviolet A(UVA) range, walls 105 a-d and 107 may be made of a highly reflectivealuminum to provide substantial reflection of UVA light. Such a materialis sold under the name 1500 G-2 and is available from ALANOD ofEnnepetal, Germany.

The light sources suitable for use in the present invention may includeany light source that is capable of providing light of a particularwavelength and intensity for treating a particular biological fluid. Forexample, light sources capable of providing white light, red light,infrared, ultraviolet A and/or B light may be used. Light drawers 60 and70 may include a single lamp or an array of multiple lamps 100. In oneembodiment, light source may include standard fluorescent lamps or bulbscapable of providing light of a wavelength in the UVA (ultraviolet A)range. Such lamps may be obtained from Sankyo Denki of Japan under theproduct code BL352. Light drawers 60 and 70 may further, optionally,include fans 109 for cooling lamps 100 and, more specifically, ends oflamps 100 at or near the lamp filaments.

As shown in FIG. 6, the ends of lamps 100 are inserted into sockets 104housed on socket panel 106. Socket panel may also serve as a printedcircuit board. Socket panel. 106 may be hinged and openable to allow foreasy access to lamps 100, easy insertion and removal of lamps 100, andin general, easier serviceability of light drawers 60 and 70.

As shown in FIG. 5, a portion of fluid treatment chamber 40 and, forthat matter, fluid carrying drawer 50, are separated from light drawers60 and 70 by glass plates 110. As shown in FIG. 5, upper glass plate 110rests on framework 38 and is, generally, held in place by clamps 112 and114. A lower glass plate 110 separating a portion of fluid carryingdrawer 50 from lower light drawer 70 may also be included. Glass plates110 are substantially translucent to light of the wavelengths used forthe treatment of biological fluid. Preferably, glass plates 110 may alsofilter unwanted light. Alternatively, a separate filter may be providedfor placement between the light source and the fluid treatment chamber40. In one specific embodiment, where treatment of a biological fluidwith UVA light is desired, glass plate 110 may be substantiallytranslucent to ultraviolet light within the range to 320-400 nm, but nottranslucent to light of a wavelength of less than about 320 nm. Suchglass plates are commercially available from Schott Glass of Yonkers,New York under the product designation B-270.

As set forth above, fluid treatment module 28 may optionally furtherinclude marker assembly 74. Marker assembly 74 may include one or moremarkers 76 a-76 d for marking containers within fluid treatment chamber.One or more markers 76 may be provided to mark containers at differentstages of the treatment. Markers 76 a-d may be punches for punchingholes into a portion of the container such as the container flap asdescribed in U.S. Pat. No. 5,557,098, which is incorporated byreference. Alternatively, and more preferably, markers may be stampersfor stamping designated portions of a container with ink. Such markersare commercially available from Trodat of Wels, Austria under theproduct name Printy 4911.

As shown in FIG. 11, marker assembly 74 may include a plurality ofmarkers 76 a-d for marking a plurality of containers during differentstages of the light treatment. Markers 76 a-d may be attached to abracket 78, which includes a slide 114. Slide 114 is suspended from andmovable within track 116 which is attached to the interior framework 38of light box 10. Thus the entire assembly 74 can be withdrawn from fluidtreatment module 28 for reinking, replacement of markers 76 or forgeneral servicing as shown in FIG. 5.

As shown in FIG. 12, each individual marker unit includes a marker drivemotor 120 that moves markers 76 up and down through gear 122, gear 124,lead screw 128, lead nut 126, bracket 130 and spring 132. Movement ofgears 122 and 124 actuates movement of lead screw 128 and causesdownward and/or upward movement of lead nut 126, bracket 130 andconsequently marker 76.

Fluid treatment module 28 includes blower 134 which provides air flowinto fluid treatment chamber 40 and fluid containers and thus, providesfor temperature control of fluid treatment chamber 40 (FIG. 5). Blower134 receives ambient air through an opening in bottom wall 16 locatedbelow blower 134. Blower 134 may be provided with a filter to preventdust from entering fluid treatment module 26. In addition to providingair to fluid treatment chamber 50, air from blower 134 may also passthrough opening 136 of fluid treatment module 28 and a perforation oropening 136 a in control module 26, as seen, for example in FIGS. 2 and4. In addition, fluid treatment module 26 may be provided with an airflow sensor for monitoring air movement. As shown in FIG. 5, sensor 135may be located at blower 134 or in close proximity thereto in fluidtreatment module 26. A temperature sensor 135 disposed in light box 10senses the ambient temperature. Thus, if the ambient temperature risesabove a predetermined threshold temperature, such as may occur if blower134 fails, the treatment procedure will be terminated and the containerof biological fluids will be marked or identified as unusable.

Returning to the fluid treatment module 28 and more specifically fluidcarrying drawer 50, as shown in FIGS. 5 and 13, fluid carrying drawer 50may include a tray 90 for holding one or more containers of biologicalfluid. Tray 90, shown in FIG. 7, may be placed within the cavity 88 ofthe fluid carrying drawer 50 (FIG. 8). In one embodiment, tray 90 may bemade of a molded plastic material. Where the biological fluid is treatedfrom two sides, the molded plastic material should be sufficientlytranslucent to the light provided by the lamps 100. Suitable materialsfor tray 90 include acrylic polymers such as polymethyl methacrylate(PMMA) or members of the polyolefin family such as methylpentenecopolymer. Such materials are available from many sources including CYROIndustries of Rockaway, N.J. under the product name ACRYLITE® OP4 orfrom Mitsui Plastics of White Plains, N.Y. under the name TPX.

Where one or more containers are to be treated, tray 90 may be dividedinto a first portion 180 and a second portion 182 separated by dividingwall 184. As shown in FIG. 27, at least a portion of dividing wall 184may be made of or covered with a reflective material of the typedescribed above. In a preferred embodiment, the portion of dividing wallthat separates first compartments 188 (described below) is reflective. Areflective divider provides improved and more uniform distribution oflight to the fluid containers. As shown in FIG. 7, tray 90 may includeretaining tabs 186 for placing a slit or other aperture of a biologicalfluid container 206 over tab 186 to limit movement of the containerwithin tray 90 and ensure that the container is substantially within thefield of light provided by the light source. The volume of tray 90should be sufficient to hold at least the entire volume of biologicalfluid contained within the containers so as to minimize the risk that,in the event of container leakage, liquid will overflow and contact theelectrical and mechanical components of light box 10, even duringagitation.

Where the biological container is part of an integrated fluid processingset, tray 90 may be compartmentalized to provide separate compartmentsfor the container undergoing treatment on the one hand, and theremainder or a portion of the remainder of the disposable processingset, on the other hand. As shown for example, in FIG. 7, first portion180 and second portion 182 each include a first compartment 188 andsecond compartment 190 separated by discontinuous wall 192. Firstcompartment 188 may hold a container of biological fluid 206 and thesecond compartment may hold the remaining components of the fluidprocessing set. A slot in the wall 192 accommodates the tubing thatconnects container 206 with the remainder of the disposable processingset. The slot may also assist in limiting movement of container 206within tray 90. Tray 90 or second compartment 190 of tray may furtherinclude container retaining tabs or pegs 193 to hold in place thecontainers in the second compartment and/or limit movement of suchcontainers within tray 90. Alternatively, pegs 193 may be located ondrawer 50, as shown in FIG. 26.

When the tray 90 with disposable processing set is introduced into fluidtreatment chamber 50, container 206 within a first compartment 188 ispositioned substantially within the field of light provided by the lightsource. The remainder of the disposable processing set and/or containerswithin a second compartment 190 are outside the field light, preferablyheld in place by tray cover 380, described below. In the embodimentwhere marker assembly 74 is provided, containers within secondcompartment 190 are aligned substantially with marker assembly 74 asshown in FIGS. 4 and 5. Thus, the status of the treatment may beindicated on the other containers of the processing set within thesecond compartment 190 by markers 76 a-d.

In an embodiment where the light box does not include a marker assembly,drawer 50 may include a cover 380 of the type shown in FIGS. 26-28.Cover 380 holds in place containers within second compartment 190. Asshown in FIG. 28, cover 380 may be hingedly attached to drawer 50 andflipped over compartments 190 prior to the illumination process.

As shown in FIG. 28, cover 380 may include latch 382 for securing cover380 to dividing wall 184 of tray 90. Cover 380 may also include aplurality of apertures 384 aligned with bag placement sensors (describedbelow). Cover 380 can be made of any suitable material which is nottranslucent to light from light sources. Preferably, cover 380 is madeof aluminum.

Light box 10 may include sensors for detecting different conditionsduring the pretreatment and treatment processes. The sensors relaysignals to the microprocessor of the light box 10 that is housed withincontrol module 26. As shown for example in FIG. 14, sensors (e.g., 404,430) send signals through the sensor input/output board 33 whichtranslates the signal into a format that is understandable bymicroprocessor 160. The computer alerts the operator, either by anaudible alarm or a message on the display screen 37. The operator may,in response to the alarm or message, take action through keypad 39.Alternatively, in response to certain alarm conditions, the controlsystem may be preprogrammed to automatically take action; such as aterminate treatment, if necessary.

For example, light box 10 may include internal light intensity sensors404 for measuring the intensity of light provided by the lamps 100 tofluid treatment chamber 50. In the event that the light intensityprovided by lamps 100 is insufficient for the desired treatment, sensors404 send signals through input/output board 33 (FIG. 14) tomicroprocessor 160 as described above.

In one embodiment, light intensity sensors 404 may be located within thelight chambers 101 and 103 of light drawers 60 and 70 (FIG. 6). In oneembodiment, light drawer 60 and/or 70 include a light intensity sensorsubassembly 402 on the underside of drawer 60 and/or 70. As shown inFIG. 6 a, subassembly 402 includes two or more sensors 404 attachedthereon and placed within sensor windows 406 located in the bottom wall107 of drawers 60 and/or 70. Sensor windows 406 allow light from lamps100 to pass through and contact sensors 404. Sensors 404 may include orbe used with one or more filters to filter out unwanted light. Morespecifically, where light box 10 is used to activate a photochemicalagent, it may be desirable that the filters used in association withsensors 404 have a maximum sensitivity in the wavelength range thatsubstantially matches the wavelength range within which the particularphotochemical agent is most effectively activated (i.e., the “actioncurve”). This allows sensors 404 to detect the effectiveness ofphotochemical activation. Sensors 404 are available, for example, fromMicropac Industries, Inc. of Garland, Tex. under part number 61120.Filters are available from a variety of sources such as Schott TechnicalGlass of Duryea, Pa.

A fluid carrying drawer sensor 144 may be included for monitoring theposition of fluid carrying drawer within fluid treatment chamber 40.Fluid carrying drawer positioning sensor 144 ensures that the drawer 50is in a fully closed position and therefore, that containers ofbiological fluid are substantially within the field of light provided bylamps 100. If the drawer is not in a fully closed position, sensor 144sends a signal to the microprocessor, alerting the operator andpreventing treatment from proceeding.

Light box 10 may, optionally, further include temperature sensors 145for either directly or indirectly monitoring and measuring thetemperature within fluid treatment chamber 40. Temperature sensor may bedisposed within the fluid treatment chamber 40 or, as shown in FIGS. 4and 5, may be disposed on the exterior of light box 10 to measure theambient temperature of the outside environment. For example, ambienttemperature sensor 145 may be located anywhere on the surface of lightbox 10. In one embodiment, as shown in FIGS. 1 and 2, ambienttemperature sensor 145 is placed at or near control module 26. Ambienttemperature sensor 145 provides an indication of the air temperaturebeing delivered to fluid treatment chamber by blower 134. In the eventthat the temperature falls outside of a predetermined temperature range,the ambient temperature sensor sends a signal to the microprocessor asgenerally described above, which alerts the operator that thetemperature is approaching or has exceeded its limit. Accordingly, theoperator and/or instrument may take further action.

Additional sensors may be provided, including a sensor for monitoringthe agitation provided by the agitation assembly. In an embodiment oflight box 10 that includes marker sub-assembly 74, sensor 430 may beattached to marker subassembly 74, as shown in FIG. 11A, and measuresmovement of the agitation assembly described above. In an embodimentwhere light box 10 does not include marker sub-assembly 74, sensor 430may be attached to marker subassembly 74 In one embodiment, sensor 430may include an infrared source such as, but not limited to a lightemitting diode (LED) or laser that contacts a selected reflectiveportion of the agitation assembly. If sensor 430 does not detectreflection or does not detect reflection at the predetermined frequency,it signals the microprocessor accordingly.

A preferred embodiment of a motion sensor arrangement for the agitatorsystem is illustrated in FIG. 27. This agitator motion sensor includes alight emitter 386, such as a lamp, a light emitting diode, a laserdiode, or the like, disposed on one side of tray 90. An aperture 388 isdefined through one edge of cover 380 and a light detector 385, such asa photo-diode, photo-transistor, photo-multiplier tube, or the like, isdisposed on the opposite side of cover 380 from the light emitter 386.When aperture 388 is in alignment with light emitter 386 and with lightdetector 385, a brief electronic pulse will be generated by lightdetector 385 when light is transmitted through aperture 388 to lightdetector 385. Based upon the rate of pulses, the speed of agitation canbe determined or confirmed. Also, if no pulses are received, it can beassumed that the agitator system is not in motion.

Light box 10 may also include a sensor 440 to detect whether the frontdoor of the light box is closed during treatment. Door sensor may be amagnetic switch that detects contact between door 36 and magnetic plate441 shown in FIG. 3. Also, plunger switch 36 a (FIG. 4) is pressed whendoor 36 is closed. If door 36 is open, plunger switch 36 a serves as anelectrical cut off. If, the door is open, the system will not permit thetreatment to proceed. Alternatively, light box 10 may include a doorlock 388. Door lock 388 may include a solenoid that establishes contactwith a pin on door 36 and ensures that door 36 remains locked duringtreatment.

Light box 10 may also include sensors 450 for determining whethercontainers are in position for marking by markers 76. In the embodimentwherein light box 10 includes marker sub-assembly 74, shown in FIG. 11A,sensors 450 may be attached to markers 76 and may include opticalreceivers aligned with light emitting diodes (LED) (not shown) typicallylocated below fluid carrying tray 90. The labels of containers placedwithin the second compartment 190 of tray 90 or a holder or organizerused to hold together containers in compartment 190, prevent opticalreceiver 450 from receiving the LED signal, indicating the presence of acontainer. Conversely, if sensor 450 receives the signal, this indicatesthat no container is present and the marker will not be activated. Inaddition, each marker 76 a-d may include a microswitch (shown as 470 inFIG. 14) to detect whether movement of the marker has occurred and toprevent mechanical failure or damage to the parts that make up themarker.

Returning to FIG. 27, in an embodiment where light box 10 does notinclude marker sub-assembly 74, a pair of light emitters 383 and 384 maybe disposed on one side of an edge of cover 380. A pair of lightdetectors 381 and 382 may be disposed on an opposite side of the edge ofcover 380. A pair of apertures 387 and 389 is defined through the edgeof tray 90. When a container is present, light from light emitters 383and 384 is obstructed from passing through apertures 387 and 388 tolight detectors 381 and 382. However, when no container is present,light will pass through one or both of apertures 387 and 389, andcorresponding light detectors 381 and/or 382 will generate a signal. Anysuch signals indicate that no container is present and the instrumentwill either alert the operator and/or terminate further processing.

The electronic circuitry, generally designated 600, for controllinglight box 10 is illustrated in block diagram format in FIG. 33. Acomputer printed circuit board (PCB) 602 preferably includes a 486DX4compatible central processing unit (CPU), or microprocessor, 603typically operating at 100 MHz, or more, to provide, and to service, amultiplicity of functions. A DRAM module 604 provides memory for CPU603, which may be, by way of example, about 32 Megabytes. Flash memorymay be added to a compact flash socket 605. Preferably, about 32Megabytes of flash memory is provided. VGA BIOS 606 is programmable tosupport displays on display screen 37 on control panel 32 (FIGS. 1 and2). A VGA port 607 provides video information to display screen 37 oncontrol panel 32 via output lines 608. A PC/104 port provides an ISA Bus610 for transferring information to and from computer PCB 602.

Four RS232 compatible ports 612 through 615 provide serial informationtransfer, such as from bar code reader 41. One of the RS232 ports isconfigurable as an RS 485 port, if desired. Port 615 is at the rearpanel of the light box 10, and ports 612 and 613 are spares. Forexample, one of spare ports 612 or 613 may be used for a label printer.A printer port 618 on computer PCB 602 is brought out to the back panelof light box 10 as a port 619 for connection to a printer. Similarly, anEthernet port 620 on computer PCB 602 is provided as an Ethernet port621 on the back panel. Computer PCB 602 is preferably an off-the-shelfcomputer board, such as that commercially available from AmproComputers, Inc., San Jose, Calif. under part number LB3-486e. Moreinformation about this and comparable computer PCBs is available atinternet site www.ampro.com, which is incorporated herein in byreference in its entirety.

An interface PCB 606 directly or indirectly interfaces computer PCB 602with most 6f the other electrical apparatus, such as lamps, sensors,displays and so forth. Interface PCB 606 is subdivided into severalportions. An LCD portion 624 receives video and control signals fromcomputer PCB via lines 608 and provides control signals to a back lightinverter (BLI) PCB 626 to control and to supply power for thebacklighting of display panel 37. LCD portion 624 also supplies videoand control signals, and power, via lines 627 to display panel 37. Akeypad and LED portion 630 receives inputs from keypad 39 at the userinterface 32, and sends such inputs to computer PCB 602 via ISA bus 610.

A light sensor portion 634 of interface PCB 606 bi-directionallycommunicates with a relay PCB 640 via a plurality of lines 635 toprovide control output signals and to receive sensor input signals. Amiscellaneous sensors portion 636 and a relay control portion 637bi-directionally communicate with relay PCB 640 via a plurality of lines638 to provide control output signals and to receive sensor inputsignals.

Interface PCB 606 also supplies operating power to the other PCBs.Interface PCB 606 receives +5 Vdc and +12 Vdc at a connector 622 and +24Vdc at a connector 623, all from a power supply 167. Relay PCB 640 issupplied with +5 Vdc and +24 Vdc on certain of lines 638, front paneluser interface 37 is supplied with +5 Vdc on one of lines 627, BLI PCB626 is supplied with +5 Vdc on one of lines 625 and computer PCB issupplied with +5 Vdc and +12 Vdc on certain of lines 610, all frominterface PCB 606. In addition, relay PCB 640 directly receives 240 Vacfrom the power supply 167 at a connector 641 to supply power to theshaker motor 92.

Relay PCB 640 controls the application of power to upper lamp ballasts645 and lower lamp ballasts 646, such as with electronic relays locatedon relay PCB 640, to supply operating power to upper lamps 100 and tolower lamps 100 under the influence of control signals from light sensorinterface 634 on interface PCB 606. Light sensor circuitry shown in FIG.34 is disposed on upper and lower light sensor PCBs 643 and 644 andprovides signals to relay PCB 640 that are indicative of the intensityof illumination provided by the upper and lower lamps, respectively.Relay PCB 640 also controls the application of power to shaker motor 647and blower fan 648, such as with electronic relays, in accordance withcontrol signals from relay control interface 637 on interface PCB 606.Relay PCB 640 routes signals from door solenoid 648 and miscellaneoussensors 649 to miscellaneous sensors interface 636 on interface PCB 606.

As previously explained, light box 10 has two light chambers 42 and 43for treating biological fluids in either or both chambers. Two lightarrays consisting of four lamps 100 are disposed in an upper positionand in a lower position in each chamber for a total of 16 lamps, as seenin FIG. 34. A light sensing system, for sensing the intensity of theillumination from lamps 100, is generally designated 650. Disposedadjacently to the upper lamp arrays in chambers 42 and 43 is upper lightsensor PCB 643. Lower light sensor PCB 644 is similarly adjacentlydisposed to lower light arrays. Light sensors 404 are positioned onupper and lower light sensor PCBs 643 and 644, respectively, betweenpairs of lamps 100 such that each sensor monitors the illumination levelof two adjacent lamps. In this respect, each light sensor is preferablylocated midway between a pair of monitored lamps 100. Light sensors 404provide a frequency output generally in the range of 10 Hz to 1 MHzdepending upon the sensed irradiation level. In this application,sensors 404 preferably operate near a mid-range, such as in about the 1KHz to 100 KHz range, for example.

Circuitry associated with each upper or lower light sensor PCB 643 or644, and which constitutes a portion of light sensing system 650, isshown in greater detail in FIG. 35. The frequency outputs from upperlight sensors 404 are sent to a pair of multiplexers 651 and 652.Multiplexer 652 is a secondary or redundant multiplexer that is used toconfirm that data received from multiplexer 651 is accurate. A testcircuit 654 consists of an oscillator 655 that has its frequency dividedby a divider 656 to provide three test or reference frequencies on threelines 657, which are provided as inputs to multiplexers 651 and 652. Forexample, these test frequencies may be about 230 KHz, 115 KHz and 57.5KHz. The power supply +5 Vdc is also provided as an input tomultiplexers 651 and 652 to monitor the power supply for any undesirednoise that could interfere with the signals from the light sensors.Three address selection lines 658, including A0, A1 and A2, are used tocause multiplexers 651 or 652 to alternately sample one of the outputsfrom the four light sensors, one of the three test frequencies or thepower supply voltage. For example, the sampling periods may be about 15milliseconds. These address selection bits on lines 658 are generated bya programmable logic device (PLD) 680 on interface PCB 606 and suppliedto upper light sensor PCB by lines 669 and to lower light sensor PCB bylines 668. Lower light sensors 404, multiplexers 660 and 661 and testcircuit 662 on lower light sensor PCB 644 operate similarly to thecorresponding elements described on upper light sensor PCB 643 toprovide a second multiplexed frequency signal.

The outputs of multiplexers 652 and 660 are routed to a frequencycounter 670 on interface PCB 606 via lines 665 and 664. The outputs ofmultiplexers 651 and 661 are routed to frequency counter 671 also oninterface PCB 606 via lines 667 and 666. Counters 670 and 671 arecommercially available from Intel Corporation, Santa Clara, Calif. underpart number 8254. PLD 680 selects data from frequency counter 670 by achip selection line 681 or from frequency counter 671 by a chipselection line 682. Frequency counters 670 and 671 and PLD 680 share acommon data bus 683 for the transfer of data therebetween. PLD 680 thusreceives counts from counters 670 and 671 that represent the frequenciesreceived by these counters from multiplexers 651, 652, 660 and 661which, in turn, represent the illumination levels from all 16 of thelamps 100 in light box 10. PLD 680 provides this lamp illumination datato computer PCB 602 on data busses 687 and 688. PLD 680 essentially actsas a conduit for the count information from counters 670 and 671 tocomputer PCB 602, provides buffering of these count signals and provideschip select functions to select counter 670 or 671. Counters 670 and 671can issue interrupt requests to PLD 680 on lines 684 and 685,respectively. PLD 680 can also issue interrupt requests to computer PCB602 on a line 686 and control signals are received by PLD 680 fromcomputer PCB 602 on one or more lines 689. PLD 680 is commerciallyavailable, for example, from Altera Corporation of San Jose, Calif.under part number EPM7128S.

Sensor read software 690 enables CPU 603 on computer PCB 602 to read thedata sent from PLD 680 on data busses 687 and 688. Independentillumination software 691 monitors the data for any malfunction orirregularity. For example, if the illumination data from any lightsensor 404 is below a defined threshold level, one of the lamps 100 mayhave failed or is providing insufficient illumination. In this instance,a message will be displayed on display 37 to replace one or more lamps100.

Energy measurement software 692 measures the illumination level suppliedby lamps 100, as by analyzing the frequency counts from PLD 480, andthen essentially integrating the measured illumination level over timeuntil the predetermined illumination dose for the biological fluid beingtreated in light box 10 is reached. Software 692 may recalculate thelight intensities about every second, for example. Frequentrecalculations are preferred because the light intensity from lamps 100changes with temperature. Based upon these continuous recalculations oflight intensity, energy measurement software 692 also determines thecurrent illumination dose that the biological fluid has been subjectedto since the initiation of treatment. Software 692 is essentiallyintegrating the light intensity in real time to determine the currentillumination dose. Software 692 can similarly estimate how muchadditional time is required, based upon currently measured lightintensities, to reach the desired illumination dose. Upon reaching thedosage entered by the user at the beginning of treatment, software 692causes illumination to cease and the user is advised that treatment iscompleted.

Software 692 also preferably constantly monitors the count of the testfrequencies 657 because these frequencies are known and the countresults will confirm the signal paths and counting accuracy with respectto the frequency signals from light sensors 404. The redundant lightsensing channel provided by secondary multiplexers 652 and 661 are alsopreferably monitored to confirm the accuracy of information receivedfrom primary multiplexers 651 and 660. If the frequency count datareceived from primary multiplexers 651 and 660 are not within a certaintolerance with the data received from secondary multiplexers 652 and661, an error message will be supplied to the user, as on display 37.When the predetermined illumination dose is reached, energy measurementsoftware 692 terminates illumination in light box 10.

In addition, a portable and attachable light intensity sensing,verification and calibration device or radiometer 460 may be provided toverify light intensity provided by light box 10 and for calibration oflight box 10. Radiometer 460 may be adapted for placement within fluidtreatment chamber 40 for measuring the energy dose delivered to thebiological fluid. More specifically, radiometer 460 may be adapted forplacement within the fluid container carrying tray 90. In oneembodiment, radiometer 460 may be adapted for placement within acompartment of tray 90 such as first compartment 188 of tray 90.

As shown in FIG. 14A, radiometer 460 may include a support 465 having atop surface 467 and a bottom surface 468. Support 465 is typically aprinted circuit board. One or more sensors 469 are electrically andphysically connected to support 465. Additionally, as best seen in FIG.31, support 465 also includes data port 512.

It is known that a light source may not always uniformly emit light. Forexample, depending on the age of the lamp, the intensity of lightemitted from one part of the lamp may not be the same as the intensityemitted from another part of the lamp. Accordingly, in a preferredembodiment, as shown in FIG. 14A, radiometer 460 may include a pluralityof sensors 469 spaced across the top and/or bottom surface(s) to receivelight from different points on one or more lamps. Also, sensors 469 maybe placed on one side of support 465, but preferably are placed on boththe top surface 467 and the bottom surface 468. Top and bottom placementof sensors 469 is particularly preferred where radiometer 460 is used tomeasure light provided by two facing light sources, such as the twoarrays of lamps 100 in one of the embodiments of light box 10.

Radiometer 460 is preferably calibrated with a precision light source inaccordance with NIST standards. As seen in FIG. 29, a bar code 506 maybe placed on the edge of one of the halves 504. Bar code 506 preferablycontains information on the identity of each radiometer, such as aunique identifying number or a serial number. Also preferably includedin bar code 506 are the calibration coefficients determined during themost recent calibration of radiometer 460 for each of the sensors 469,and an expiration date by which radiometer 460 will need to berecalibrated. For example, the expiration date may be one year from thedate of the most recent calibration. Thus, reading of bar code 506 bybar code reader 41 will provide CPU 603 with information on the identityof radiometer 460, the calibration coefficients associated with thatparticular radiometer, and the date by which radiometer 460 needs to berecalibrated.

Support 465 is preferably housed in cover 501. As shown in FIG. 31,cover 501 may be made of two halves 503 and 504 that are attachedtogether. Cover 501 may include a label 506 (FIG. 29). displaying aunique bar code for each radiometer 460. As further shown in FIG. 31,radiometer also includes intermediate panels or substrates 508 and 510.Cover halves 503 and 504 and substrates 508 and 510 may be made of anyhard, commercially available molded plastic. A preferred material is aterpolymer of acrylonitrile, butyldiene and styrene (ABS). Slots incover 501 and substrates 508 and 510 are provided to accommodate sensors469.

A connector cable 516, as shown in FIG. 32, is attached to radiometer460 for electrical connection to light box 10 and, for example, to port461 (FIG. 5). This allows radiometer 460 to transmit data to thecomputer PCB 602 (FIG. 33) of light box 10, which system providesinformation to the operator and/or automatically takes action based onthe transmitted data. Radiometer 460 may also include a slit 472 (FIG.29) for placement over tab 186 (FIG. 7) in tray 90 of light box 10.

Sensors 469 are generally any device that is capable of detecting lightof selected wavelengths. These sensors are preferably robust such thatthey reproducibly detect the appropriate wavelengths accurately. In oneembodiment, these sensors may comprise a plurality of optical fibersthat absorb the selected wavelengths and channel the light into anappropriate detector. Such optical fibers can be configured toappropriate dimensions to represent the dimensions over which the lightdelivery is to be measured. An advantage of this configuration is thatthe optical fibers can cover a large percentage of the area over whichthe light delivery is to be measured. In the preferred sensorembodiment, as represented in FIG. 14A, sensors 469 in radiometer 460are preferably the same type of sensor as sensors 404 in light sensingsystem 650. Of courses, sensors 404 and 469 need to be capable ofdetecting light of the desired wavelengths. Sensors 469 may also includeor be used with filters to filter out unwanted light as substantiallydescribed above.

When used in connection with light box 10, it is preferred that thedimensions and geometry of radiometer 460 be substantially equivalent tothe dimensions of the fluid-filled containers used with light box 10.Accordingly, it is preferred that the light sensing area of radiometer460 have a height, a width and a thickness substantially equal to suchfilled containers. A radiometer with dimensions substantially equal tothe fluid-filled container provides a reliable approximation of theenergy being delivered to the fluid and of the effectiveness of thetreatment.

As set forth above, radiometer 460 may be used for light intensityverification by, for example, the operator and for calibration of lightbox 10 generally and more specifically, of internal light sensors 404.In accordance with the method of using radiometer 460 for lightintensity verification, the operator may place radiometer 460 in firstcompartment 188 of tray 90, as shown in FIG. 32. Connector cable 516 maybe pressed into strain relief tabs 474 within light box 10 (FIG. 8) or,more preferably, thread through slot 390 in drawer 50, as shown in FIG.32. The fluid carrying drawer 50 is inserted into fluid treatmentchamber 40 and door 36 is closed. Lamps 100 are turned on and the lightdelivered is measured by sensors 469 in radiometer 460. Specifically,the light measured by sensors 469 is processed by the system'smicroprocessor 603 on computer PCB 602 to provide a calibrated readingof the energy being provided to the fluid treatment chamber 40. Forexample, microprocessor 603 may use the calibrated readings of the lightlevels from each sensor 649 of radiometer 460 to calculate a calibrationcoefficient for light levels sensed by each sensor 404 on upper andlower light sensor PCBs 643 and 644. Thereafter, energy measurementsoftware 692 (FIG. 34) associated with microprocessor 603 can applythese calibration coefficients to the illumination measurements fromlight sensors 404 to provide corrected light level measurements thatwill approximate those measured by radiometer 640. The flow chart inFIG. 21A also provides information about the processes of determiningthe light intensity and determining the treatment time.

The operator can monitor the output of lamps 100 and determine anydiminishment in the lamp output by comparing the reading to a pre-setacceptable energy dose range. In addition, the readings provided bysensors 469 are also compared to the readings provided by sensors 404 todetect any diminished sensing capability of sensors 404. The process maybe repeated with the other first compartment 188.

Thus, for example if the energy dose measured by radiometer 460 issubstantially equal to the energy dose detected by sensors 404, but isoutside the pre-set dose range, this may be an indication that theoutput of lamps 100 has diminished and that lamps 100 may have to bereplaced. Alternatively, if the energy dose as measured by radiometer460 is substantially equal to the expected pre-set dose of theinstrument, but both are different from the energy dose as measured bysensors 404, this may be an indication that sensing capability ofsensors 404 has diminished. Finally, if the dose as measured by sensors404 is substantially equal to the expected pre-set dose, but differentthan the energy dose as measured by radiometer 460, this may indicatethat the sensing capability of radiometer 460 has diminished. Radiometer460 may also be used to calibrate light box 10. Radiometer 460 itselfmay be calibrated against a standard (e.g. a standard from the NationalInstitute for Standards and Technology or NIST), or by using anindependent calibration system that has been calibrated to NISTstandards.

Of course, it will be appreciated that radiometer 460 may have utilityin other applications and is not limited to use in the apparatus ormethods of the present invention. Indeed, radiometer 460 may be usedwhenever light is to be measured over an extended surface area or fromopposite directions. Radiometer 460 also has utility where it is desiredto average light intensity measurements over a surface area, includingnon-planar surfaces. It will be readily appreciated that radiometer 460could be configured with complex, non-planar surfaces, if so desired.

The components of the fluid treatment module 28 including the agitatorassembly, the light sources, the blower, the marker subassembly arepowered by power supplies in an alternative embodiment of the electroniccontrol system shown in FIG. 14. In FIG. 14, the letter “n” representsthe number of electrical or mechanical components such as sensors,lamps, ballasts etc. For example, power supplies (ballasts) 166 powerlamps 100 and are controlled by relay board and isolation transformer29. Shaker motor 92 is powered through relay board and isolationtransformer 29. Additional power supply 168 supplies power for theblower 134, light drawer fans 109, and drive motors 120 for markers 76a-d and door lock 480. Preferably, the power supply for powering thesecomponents may be approximately 24 volts DC. Power supply for poweringshaker motor may be 230V AC. Power supply 167 may supply +5 and +12volts DC to, for example, computer board 160.

Finally, light box 10 includes a programmable computer software-basedcontrol system 600 to control the operation of light box 10 that hasalready been described with reference to FIGS. 33-35. The control system600 is further generally and diagrammatically depicted in FIGS. 19-23and is described in greater detail in connection with the description ofthe method of processing and treating a biological fluid which followsthe description of the disposable processing set provided below.

b. Disposable Processing Set

Disposable processing sets useful with light box 10 are shown in FIGS.15-18. Typically, the disposable processing set will include two or moreplastic containers integrally connected by plastic tubing. At least oneof the containers should be suitable for holding the biological fluidduring light treatment. The other container should be suitable forstorage of the biological fluid after treatment. As described in moredetail below, the disposable processing set may be joined withcontainers of biological fluid, and the fluid may be transferred tocontainers of the disposable processing set. Further details about thesedisposable processing sets are described in the U.S. Patent Applicationentitled “Fluid Processing Sets and Organizers for the Same,” bearingAttorney Docket No. F8-5459CIP, filed Oct. 11, 2002, and incorporatedherein by reference, in it entirety.

One embodiment of a disposable fluid processing set 200 is shown in FIG.15. Processing set 200 includes a container 202, a container 206, acontainer 210 and a container 214. The containers may be integrallyinterconnected with tubing segments as generally shown and described indetail below. The sizes and internal volumes of containers 202, 206, 210and 214 may vary depending on the biological fluid being processed. In anon-limiting example, container 202 may be capable of holdingapproximately 5-30 ml of fluid, containers 206 and 210 approximately1000 ml and container 214 between approximately 1000-1500 ml. Of course,other desirable sizes and volumes may be used and are within the scopeof the present invention.

Where the disposable processing set is used in or as part of a pathogeninactivation treatment, container 202 may include, for example, aphotochemical agent which is mixed with the biological fluid. Examplesof such photochemical agents include psoralen compounds described inU.S. Pat. No. 5,709,991 and compounds from the family of phenothiazinedyes, such as, but not limited to, methylene blue and riboflavin.Container 202 may be made of any material suitable for holding suchphotochemical agents. One such material may be a blend of ethylenepolypropylene, polyamide and a block copolymer of ethylene and butylenewith terminal blocks of polystyrene. Containers made of such materialare available from Baxter Healthcare Corporation under the name PL2411.Container 202 includes a tubing segment 203 extending therefrom andhaving a sealed end 204. A second tubing 205 extending from container202 is integrally connected to container 206. In another embodiment, thephotochemical agent may be contained or predisposed within container206, thereby eliminating the need for a separate container 202 forholding the photochemical agent. In still another embodiment, thephotochemical agent may be combined with the biological fluid prior tojoinder to the disposable processing set. For example, the photochemicalagent may be included in a container 201 used to hold the biologicalfluid collected from a donor (FIG. 17).

Container 206 is preferably a container suitable for holding thebiological fluid during light treatment. Accordingly, it is desirablethat container 206 be made of a clear, durable, thermoplastic materialthat is translucent to light of the selected wavelength and sterilizableby known forms of sterilization including steam sterilization, gamma andelectron beam radiation. For example, where the blood product to betreated includes blood platelets or blood plasma and the treatment is tobe with light in the UVA range, container is made of a material that issubstantially translucent to UVA light and remains stable aftersterilization. Such materials may include polyvinyl chloride, but morepreferably, may be blends of thermoplastic polymers and copolymers,including general purpose polymers, elastomers and the like. One suchmaterial includes the block copolymer described above which includes acentral block of ethylene and butylene and terminal blocks ofpolystyrene. Block copolymers of the type described above are availablefrom the Shell Chemical Company under the name KRATON. The blockcopolymer may be blended with other polymers such as ultra low-densitypolyethylene (ULDPE) and ethylene vinyl acetate (EVA). Containers madeof the blended material are available from Baxter Healthcare Corporationof Deerfield, Ill. under the name PL-2410. Other thermoplastic materialsmay also be suitable for container 206, including materials includingKRATON, EVA, and polypropylene. A container made from such material isalso available from Baxter Healthcare Corporation under the name PL-732.Still other suitable materials for container 206 include fluoropolymerssuch as polytetrafluoroethylene (PTFE), PFA or copolymers including suchfluoropolymers.

Container 206 further includes a slit 207 which, as described above, maybe placed over retaining tab 186 in tray 90. Container 206 includes atubing segment 208 which may be integrally connected to a container 210.

In the pathogen inactivation of biological fluid, container 210 may, forexample, include an adsorbent material 211 for removing excessphotochemical agent or the byproducts of the photoactivation process.The adsorbent material may be contained in a semi-permeable pouch,preferably affixed to the container walls or portions thereof within theinterior chamber of container 210. The interior chamber of container 210has a volume sufficient to hold the biological fluid from container 206.Such a container and the adsorbent material are disclosed in more detailin copending patent application entitled “Plastic Containers HavingInner Pouches and Methods for Making Such Containers” which is beingfiled simultaneously herewith in the names of Mahmood Mohiuddin, GeorgeD. Cimino and Derek J. Hei, and is incorporated by reference in itsentirety. Materials such as those used in the PL-2410 and PL-732containers described above are suitable for use in container 210.

Container 210 may also include a time-sensitive tape 209. Tape 209changes color with time, thus informing the operator if the biologicalfluid has contacted the adsorbent material for a sufficient period oftime. Container 210 may be integrally connected by tubing segment 211 toanother container 214 which may be suitable for storage of thebiological fluid. As shown in FIG. 15, the portion of tubing segment 211that communicates with the interior of container 210 may include afilter 211 a to capture loose particles of adsorbent, if any.

Container 214 may include and/or be capable of receiving a label 216which may carry bar codes 222 or other indicia that provide informationabout the biological fluid. For example, bar codes 222 may identify thedonor, the product, the lot number of the biological fluid, expirationdate and the like. Container 214 may include additional bar codes orindicia 224 which are used to provide information regarding the statusor progress of the fluid treatment (described in more detail below).Container 214 may also include a slit 226 and/or apertures 228, 230 forplacement over corresponding pegs (193) on tray 90. Materials such asthose described above are suitable for use in container 214. Container214 may also include sampling pouches 214 a and access ports 214 b toallow for fluid access during later transfusion, as will be recognizedby those of ordinary skill.

In an alternative embodiment, disposable processing set may include asingle container for housing the adsorbent material of container 210 andfor storing the biological fluid, thereby combining the functions ofcontainer 210 and 214 described above.

The disposable processing set 200 described herein may further includefrangible members 230 (a-c) disposed within tubing segments as shown inFIG. 15. Frangible members 230 are broken at the appropriate time toestablish fluid communication between the containers of the processingset 200. Such frangible connectors are described in detail in U.S. Pat.No. 4,294,297 which is incorporated by reference herein. Tubing segmentsof disposable processing set 200 may further include indicators 234 aand 234 b on the tubing to indicate proper positioning of the disposableprocessing set within the tray 90 (as will be described more detailbelow) and/or to serve as indicators of where tubing is to be severedand sealed. In one embodiment, indicators 234 may be plastic ringsdisposed around tubing segments. Of course, other tubing indicatingmeans may be used.

Another embodiment of a fluid processing set is shown in FIG. 16. InFIG. 16, disposable processing set 240 also includes a container 242which carries a photochemical agent, a container 244 which holds thebiological fluid during light treatment, a container 246 which includesan adsorbent material for removing excess photochemical agent and/or thebyproducts of the photoactivation process, and a container 248 suitablefor storage of the biological fluid. Container 248 is adapted to receivelabel 249 with bar codes or other indicia and may include additionalindicia 251 including, for example, additional bar codes assubstantially described above.

In contrast to the container 210 of the earlier described embodiment,container 246 is a flow through device which includes adsorbent material212 but does not include a chamber for holding the biological fluid forany significant period of time. Such flow through devices are describedin International Publication No. WO 96/40857, which is incorporated byreference herein. Disposable processing set 240 may further include anair reservoir 256 and air sink 258. Air reservoir 256 provides air tohelp expel biological fluid from container 244 and air sink 258 receivesexcess air expelled from storage container 248 after processing. Airreservoir 256 and air sink 258 may be made of any suitable biocompatiblematerial, including the materials described above. Likewise, thecontainers of disposable processing set 240 may also be made from thematerials generally described above. Preferably, container 256 issubstantially impermeable to air.

As in the embodiment of FIG. 15, the containers of disposable processingset 240 shown in FIG. 16 may be integrally interconnected by tubingsegments 243, 245 and 247. Tubing segments may further include frangiblemembers 249 (a-c) for opening fluid communication between thecontainers.

Disposable processing set 200 (or 240) is typically provided to the userin a sealed package in a manner that is easy for the user to unpack anduse. For example, upon opening the package, it is preferred that thecontainer to be used first in the fluid processing be located near thetop of the package. For example, in the processing set 200 shown in FIG.15, container 202 would be located near the top of the package, followedby container 206, followed by the remainder of the disposable processingset that includes containers 210 and 214. In addition, if disposableprocessing set includes container 202, (or 242 in the embodiment of FIG.16) at least such container should include a separate and additionallight impermeable overwrap to protect the contents (i.e. thephotochemical agent) from exposure to light which could result inpremature activation of the photochemical agent. In one embodiment, thelight impermeable overwrap may be permanently sealed to the outer wallsof container 202.

In a preferred embodiment, containers 210 and 214 may be containedwithin or held together by a holder. Holder may be any device such as aclamp that holds together containers 210 and 214. The holder may beintegral with the disposable processing set or may be providedseparately.

More preferably, holder 260, shown in FIGS. 17-18, may be a receptacleor other shell-like holding device. In one embodiment, holder 260 mayinclude a bottom wall 262 which separates the containers 210 and 214from container 206. In a preferred embodiment, holder 260 may havesidewalls 262 and 264, a back wall 268 and includes a substantially openfront portion as shown in FIGS. 17-18. In addition, bottom wall 262 mayinclude a slot 263 to accommodate tubing that connects containers ofdisposable processing set 200. Holder 260 may also include additionalside openings 265 (shown, for example, in FIG. 17) for holding tubingsegments of container 202 prior to unpackaging of the disposableprocessing set. Holder 260 may be made of any suitable material such asbut not limited to plastic or cardboard. Preferably, holder 260 is madeof a moldable plastic material that may be sterilizable and impactresistant.

Alternative embodiments of holder 260 are shown in FIGS. 18A-18D. Asshown in FIGS. 18A-18C, holder may include two frame or partial frameportions 600 and 602. Frame portions 600 and 602 may be joined andinclude hinge 604 as shown in FIG. 18B and 18C. Alternatively, framemembers 600 and 602 may be completely separable as shown in FIG. 18D.Frame portions 600 and 602 include means for securing together the frameportions such as mating slots 605 and pins or lugs 606 as shown. Holder260 shown in FIGS. 18A-18D includes a central opening 608 to allow thelabel of a container placed within holder 260 to be exposed to theoutside environment to allow scanning by, for example, a bar code readerand/or marking by markers 76 as described below.

In one embodiment, container 210 is placed in the front portion ofholder 260, such that a label to be applied to the container 210 andother indicia on the container itself are exposed to the outsideenvironment through the open portion of holder 260 as shown in FIG. 17.For purposes of illustration, in FIGS. 17-18, label is shown as appliedto container 214. In one embodiment container 214 may not include labelat the time of use and a label may be transferred to container 214 froma container of biological fluid. Alternatively, container 214 mayinclude a label and an additional label may be transferred from acontainer of biological fluid. In any event, container 214 may be foldedin half (or tri-folded) with container 210 (also folded) placed behindcontainer 214. In addition, folded container 214 may be lightly spotwelded at its ends to keep the container folded and improvehandleability of the container. The weld should be sufficiently strongto keep container 214 in a folded position, but not so strong that undueforce applied by the user would be required to disconnect the weldedends. Spot welded ends of container 210 should release when tuggedgently by the user.

Methods of Processing and Treating Fluid

The method of processing fluid using disposable processing set 200 (or240) and treating a biological fluid with light in, for example, lightbox 10 will now be described. Although the following description will beprovided in the context of processing the biological fluid forsubsequent inactivation of pathogens in the biological fluid, it shouldbe understood that many of the steps described below may also be carriedout in other fluid processing and treating methods that do not involvepathogen inactivation. The following description will be provided usingthe disposable processing set of FIG. 15 as an example, although it willbe understood that the description may also apply to other processingsets, such as the set of FIG. 16.

In accordance with the method of processing a biological fluid such asblood using the processing set 200, a container of collected blood orbiological fluid is provided. Although the method of collection isbeyond the scope of the present application, representative methods ofcollecting blood products include the automated and manual centrifugalprocessing, separation and collection of blood products, membraneseparation of blood products and the like. One example of a centrifugalblood processing system is the AMICUS® Separator sold by BaxterHealthcare Corporation.

Regardless of the collection method, containers of the collected bloodproduct will typically bear a label that includes informationidentifying the donor, the blood product and lot numbers. Mosttypically, such information is presented in the form of one or more barcodes on the label, which can be scanned and read by bar code reader,such as bar code reader 41 of light box 10. Such labels may be removableand transferable to container 214 of the disposable processing set 200.

Typically, the collection container will include a tubing segmentextending therefrom. Accordingly, tubing from the collection container201 and tubing segment 203 from the disposable processing set 200 arebrought together and joined in a sterile manner, as shown generally inFIG. 17. A device that is useful for the sterile joinder of tubingportions is available from Terumo Corporation of Japan and sold underthe name Terumo SCD. This device heat seals two opposing tubing portionsin a sterile manner. The heat from the heat sealing kills any bacteriafrom the outside environment that may enter or reside in the tubingsegments, thereby preserving the sterility of the entire processing set.Of course, any method and apparatus for joining two tubing segmentswhile maintaining sterility may be used.

Once tubing segments have been joined, frangible member 230 a is brokento provide an open flow path from the collection container 201 to thecontainer 206 (FIG. 15). Photochemical agent from container 202 is alsoallowed to flow into container 206. After fluid transfer to container206, tubing segment may be severed and sealed and the portion of thedisposable processing set that included container 202 and the collectioncontainers 201 are discarded. Indicator 234 a provides a reference pointas to where the tubing is to be severed. It is preferable that theindicator be placed as close as possible to the container 206 so thatmost of the biological fluid is retained within container 206 where itis most likely to be mixed and treated.

Before or after placement of the disposable processing set in tray 90,operator may scan the label and other container indicia with bar codereader 41. Bar codes 222 on the main container label 216 or thecontainer itself provide the instrument with information regarding thebiological fluid to be treated. Based on the data, the light treatinginstrument or operator prescribes the light dosage and then calculatesthe duration of the treatment.

Container 206 of disposable processing set 200 is typically placed infirst compartment of tray 90. Slit 207 in container 206 is placed overretaining tab 186 in first compartment 188 and holder 260 withcontainers placed therein is placed within the second compartment 190 oftray 90. Slits and/or apertures in container 216 are likewise placedover retaining tabs or pegs 193 in second compartment 190. Tubingconnecting container 206 with container 210 (and/or 214) may be pressedinto the slot in wall 192. It is preferable that the tubing bepositioned parallel to the direction of the side-to-side oscillationprovided by the agitator assembly described above. This further ensuresthat any fluid within tubing segment 208 is also mixed. Indicator 234 bnot only serves as a reference point for severance of the tubing butalso serves as a reference point for container placement by ensuringthat substantially the entire container and biological fluid therein iswithin the field of light. The indicator has a diameter greater than thewidth of the slot.

Once the containers are in their respective compartments of tray 90,fluid carrying drawer 50 is closed. As set forth above, plunger switch36 a (FIG. 4) is pressed when door 36 is closed. If door 36 is open,plunger switch 36 a serves as an electrical cut off. If, the door isopen, the system will not permit the treatment to proceed.

Light box 10 includes a programmable computer software-based controlsystem to control the operation of light box 10. The control system isgenerally and diagrammatically depicted in FIGS. 19-23. As shown inFIGS. 19-23, the, system tests, monitors and controls various aspects ofthe light box 10 and treatment operation such as the start up, containerloading, container treatment and container unloading stages of the lightbox operation. The control system allows the operator to take action oradvises the operator of the treatment status through either analphanumeric or a graphical user interface displayed on screen 37. Thevarious functions may be initiated by the operator through control panelor automatically by the control system itself.

For example as shown in FIG. 19, after the operator has turned on theinstrument (step 700), the control system will initiate a series ofsteps including checking for file system integrity 700 a, loading thesoftware 700 b, displaying the graphical user interface (GUI) screen701, and continuing to initialize 702 the light box 10 until a screen isgenerated requesting the user to log in 703. After the user logs in, themain menu 704 is displayed. The operator may then select from the seriesof available functions 705 including the treatment function 706, theprint function 707 or the illuminate settings 708. Alternatively, theoperator may choose the exit function 712 to exit the system. Diagnosticchecks 710 may also be selected and performed, typically by a servicetechnician.

If the treatment function 706 in FIG. 19 is selected, the controlsystem, through the programmed software will automatically determine iftreatment is appropriate 713 and more particularly, if light box 10 isprepared for treatment as shown in FIG. 20A. Thus, for example, if thesystem detects a failure in the light source, or a failure in one of thesensors or other equipment, an error message 714 will be displayed andthe user will be requested to press the enter 714 a option. Treatmentwill then not be enabled and will not proceed until the condition isremedied. If treatment is enabled however, the system will thendetermine if treatment was otherwise cancelled 715. If not, the systemwill prompt the operator to input the container (i.e. biological fluid)information 716. Container information may be input manually or byscanning bar codes 222 on, for example, container 214 shown in FIG. 15.The system again determines if the treatment process has been cancelled.If the data from the bag information entry in step 716 is valid at step718, the system proceeds to the next function or phase as generallyshown in FIG. 20B.

As shown in FIG. 20B, the control system displays additional options forthe operator to select at step 719. For example, the operator mayproceed to treatment of the container, request treatment of a secondcontainer or cancel the operation entirely as shown at step 720. At step719, the user may elect to return or to enter the next selection. If“Bag 2” option is selected at step 719 a, the operator is againrequested to input container information at step 722 and the system willrepeat the steps generally described above before commencing thetreatment process at step 724 a. If treatment on a single container isto be performed, the operator selects the treatment function at step324, which is described in more detail below. When the treatment processat step 724 is finished, the system prompts the user for anothertreatment. If another treatment is selected at step 726, the systemreturns to point A in FIG. 20A to input the new bag information, step716, and to determine if the new bag information is valid, step 718,while continuing to permit treatment to be cancelled at steps 715 and717.

After containers have been placed into tray 90, to commence treatmentthe system activates the light source(s) 100, shaker motor 92 and fansas shown in step 728 of FIG. 21. The instrument may display, forverification by the operator, information regarding the fluid to betreated and the treatment process generally, as at step 730. Forexample, in one embodiment, the instrument may display, thepredetermined target dose of energy to be applied to containers, theselected treatment time and a running value of the dosage percent beingapplied to the biological fluid during the treatment as shown in step730. Treatment will continue unless terminated by the operator orautomatically terminated by the instrument in response to an alarmcondition.

In one embodiment, container may be marked by markers 76 at thebeginning of treatment and after treatment is completed. The marks madeby marker 76 obliterate or otherwise masks the bar code, making itunreadable. Thus, a container with two masked bar codes 224 indicatesthat treatment has been successfully completed. On the other hand, ifonly one of the bar codes 224 has been masked, this serves as anindication that treatment was not successfully completed and thecontainer may have to be discarded. Masking of bar codes 224 by markers76 also ensures that a treated container will not be treated again.

During treatment, the system performs an energy calculation at step 732,which is computed by multiplying the light intensity sensor readings bypreselected calibration factors, averaging the readings across thesensors in the same chamber and plane and adding the reading receivedfor planes in the same chamber. The control system further verifies thetreatment status at step 734. If treatment is completed at step 735, thesystem will check the keypad at step 735 a and determine if the stop keywas pressed at step 735 b before turning off lamps 100 as shown at step736.

The system may automatically update information on the lamp life asshown at step 737 and update container records at step 738. Controlsystem may continue to power shaker motor 92 until terminated. Theresults are preferably transmitted to a microprocessor or centralprocessing unit (CPU) 603 on computer board 602 (FIG. 33). Aftertreatment, the system will prompt the operator to unload containers atstep 742 and may prompt the user to perform another treatment, ifdesired, as at step 725 in FIG. 20B. The process may be repeated asgenerally described above.

The processes of determining the light intensity, determining thecurrent energy dose and determining the treatment time based upon apredetermined or target energy dose is shown in the flow chart of FIG.21A. This corresponds, in part, to the energy calculation step 732 inFIG. 21. It is assumed that treatment has been initiated at step 724,which also corresponds to steps 724 or 724 a in FIG. 20B. When treatmentis initiated, lamps 100 are illuminated at step 770. Light sensors 404at step 771 make a measurement of the light intensity from lamps 100.Light sensors 404 convert the measured illumination level into a signalwith a frequency that is related to the sensed light intensity at step771. At step 772, the signals from each sensor 404 are combined by amultiplexer into a multiplexed frequency signal. At step 773, thefrequencies of each sensor in the multiplexed signal are counted toprovide a count that represents a composite of the illumination levelsmeasured each for each light sensor. The count of the test frequencysignals 657 is then checked at step 774 to determine the accuracy of thecounted test frequency signals from step 773. Since the frequencies oftest signals 657 are known, the count of these frequencies will confirmthe accuracy of the information counted by the counter. This in turn,will determine the reliability of the count of the sensor signals fromstep 773. At step 775, the counts of the sensor signals from step 773,and the count of the test frequencies from step 774, are compared tocorresponding counts from a secondary or redundant sensing circuit, toconfirm that the counts from the primary sensing circuit are valid. Atstep 776, calibration coefficients are applied to each sensor count byCPU 603 to provide a corrected signal count. These calibrationcoefficients are defined .during the calibration procedure, as will beexplained below in FIG. 21B. With a corrected signal count, CPU 603 candetermine the corresponding light intensity level in light box 10 atstep 777. The light sensing system typically measures the lightintensity about once every second. Using the corrected light intensitymeasurements, CPU 603 continuously updates the current energy dose thathas been delivered to one or both of treatment chambers 42 and/or 44.Based upon the current energy dose and the current correctedillumination level, CPU can determine the remaining treatment time aswell as the total treatment time, at step 779, needed to deliver thetarget dose, which was identified as one of the treatment parameters atstep 730 in FIG. 21. When target dose is reached, treatment isterminated and illumination ceases, at step 779 a.

The process of calibrating the light box 10 with a pair of radiometers460 is illustrated in FIG. 21B. The user first selects the calibrationmode at step 780. Preferably, a bar code on radiometer 460 is firstscanned to identify the radiometer being used at step 781. As previouslyexplained this bar code identifies radiometer 460 by serial number orthe like, provides calibration codes, such as for each sensor 469 inradiometer 460, and also provides an expiration date before whichradiometer 460 will need recalibration. The radiometer calibration codesare provided to CPU 603 for use in correcting light intensitymeasurements made by the radiometer. The user then places radiometer 460in one of the compartments of tray 90 such as the compartment thatcorresponds to first chamber 42 of light box 10, as in step 782.Preferably, the previously described agitator system is started so thatthe radiometer measures light intensities from lamps 100 as ifradiometer 460 is a biological fluid under treatment. As previouslydescribed and as shown in FIG. 14A, radiometer 460 has eight lightsensors 469 disposed on each side, with four sensors located near thecorners and the remaining four sensors located more centrally betweenthe four corners. Note that radiometer 460 will be measuring lightintensity as actually received by a biological fluid after beingfiltered by any filters and as received after light transmission throughtray 90 from the lower lamps 100. The light intensities measured byradiometer 460 are therefore more accurate than the light intensitiesmeasured by light sensors 404, which are disposed on the opposite sidesof lamps 100 from radiometer 460. Radiometer 460 is thus able to moreaccurately measure light intensity in tray 90 where biological fluidsare placed for treatment. It is therefore desirable to calibrate lightsensing system 650 to measure light intensity received at tray 90similarly to that measured by radiometer 460.

CPU 603 receives data from each sensor 469 in radiometer 640 to measurethe light intensity in step 783. At the same time, CPU 603 receives datafrom both upper and lower light sensors 404 in step 784, whichcorresponds to steps 771-773 in FIG. 21A. In step 785, CPU 603calculates a calibration coefficient for each sensor 404 based upon thecorrected illumination intensity readings from radiometer 460 and theuncorrected illumination intensities from illumination sensing system650.

Calibration coefficient or correction coefficient means any number orset of numbers that is used to correct measured illumination intensitiesto within a predefined tolerance of NIST standards. Thus, a generalobjective is to transfer the more accurate illumination measurementcapabilities of the pre-calibrated radiometer 460 when disposed intreatment chambers 42 or 44 to the more remotely located light sensingsystem 650 such that light sensing system 650 will measure lightintensities in chambers 42 and 44 in a manner similar to that ofradiometer 460 when disposed therein. These calibration coefficients arepreferably linear scaling factors that enable the light sensing system650 to emulate the light measuring accuracy of radiometer 460 in thetreatment chambers. These calibration coefficients, as determined instep 785, are temporarily stored in memory for future use.

At the conclusion of the calibration procedure with a first radiometer460, the user will be prompted to again calibrate the first chamber 42with a second radiometer 460. Use of a second radiometer is preferred toconfirm the calibration results obtained from the first radiometer. Theuser scans a bar code on the second radiometer so that light box 10 canconfirm that a different radiometer is being used. Steps 782-785 arerepeated with the second radiometer. If the calibration results from thesecond radiometer at step 785 are within a certain tolerance, such asabout 10 per cent, the calibration coefficient results are saved inmemory, at step 787 for use in obtaining corrected light intensitymeasurements. If the results are not within the defined tolerance, it isassumed that one of the two radiometers is faulty and the user isinstructed to return both radiometers for service. In this instance,none of the calibration coefficients is saved for use in calculating thelight intensities, and the calibration coefficients from the last priorrecalibration procedure continue to be used.

This ends the calibration procedure for the first compartment of thelight box 10 at step 788, and steps 781-787 are preferably repeated tocalibrate the light intensity measurements in the second compartment.

Treatment time and energy dosage will vary depending on the biologicalfluid to be treated. For example, the treatment time may be at least oneminute but may also be less than one minute. Where light box 10 is usedfor the pathogen inactivation of biological fluid, the treatment maytypically be anywhere between 1-30 minutes. For example, for thepathogen inactivation of blood platelets, treatment is typically between1-10 minutes, but more typically approximately 3-4 minutes. For thepathogen inactivation, of blood plasma, treatment may also preferably beapproximately 3-4 minutes.

Energy per unit area, or energy flux, is the product of power per unitarea or, in the case of radiant flux, at the target, and the time ofexposure. Accordingly, the amount of energy per unit area delivered tothe target (for example, in one embodiment, the biological fluid) willvary with the duration of exposure and the irradiance—the radiant powerper unit area incident on the target. In one embodiment the totalradiant energy flux delivered may be between approximately 1-100 J/cm2measured across a wavelength range of between approximately 300-700 nm.However, any useful wavelength that activates photochemical agents maybe used. In general, light box 10 can be retrofitted for variousillumination frequencies to illuminate treatment targets in treatmentchamber 40, including those light frequencies outside of the range of300-700 nm.

In another embodiment, where the light source provides light generallyin the ultraviolet range, the total radiant energy flux delivered to thebiological fluid may preferably be between 1-20 Joules/cm² measuredacross a wavelength range of between approximately 320-400 nm. In onespecific embodiment, the total radiant energy flux delivered to bloodplatelets or blood plasma may be between approximately 1-5 J/cm2 andmore typically approximately 3-4 J/cm² measured across a wavelengthrange of between approximately 320-400 nm. Preferably, the energy shouldnot be outside the predetermined range in that excess heat generatedwithin fluid treatment chamber 40 is to be avoided. For light treatmentof blood platelets and blood plasma, for example, temperature withinchamber 40 should typically not exceed 37 C. If an external temperaturesensor of the type described above is used, the ambient temperatureshould be between 18-30 C.

During treatment, tray 90 is preferably agitated at a preset frequency.Of course, the frequency should not be so great so as to harm thebiological fluid or components thereof. Typically, the tray 90 may beagitated between approximately 40-100 cycles/min and for bloodplatelets, more preferably, between approximately 40-80 cycles/perminute. A cycle is defined as one complete back and forth oscillation ofdrawer 80. Additionally, it may be desirable for agitation may continuefor up to 30 minutes after blood platelets have been treated with thedesired target light dose, i.e., after illumination in the light box 10is terminated.

Once treatment has been successfully completed, fluid from container 206may be transferred to container 210 by breaking frangible number 230 band opening the flow path between the containers 206 and 210 (FIG. 15).Once inside container 210, the biological fluid is allowed to contactthe adsorbent material for a selected period of time. As noted above, inone embodiment, container 210 may also include time-sensitive tabs 209that change color over time. This way, the operator will know if thecontainer has been in contact with the adsorbent material for theappropriate period of time. The adsorbent material is selected to removeany residual photochemical agent or any by products of the photochemicalprocess that may have been included in the biological fluid. Theadsorbent material may include polystyrene beads or activated charcoalor other adsorbent material. Such materials are described in greaterdetail in International Publication No. WO 96/40857, incorporated byreference herein.

Alternatively, in the disposable processing set 240 shown in FIG. 16,the biological fluid may simply pass-through container 246 withoutresiding for any significant time, within the container. The details ofthe removal process and materials used are described in theabove-identified International Publication No. WO96/40857.

The residence time, if any, of the biological fluid in container 210 (or246) will be anywhere between approximately 30 seconds and 7 days. Inaddition, during contact of the biological fluid with the adsorbentmaterial of container 210, it may be desirable to shake or otherwiseagitate container 210 to ensure maximum contact with the adsorbentmaterial.

Regardless of which disposable set is used, after the required residencetime, if any, the biological fluid may be transferred to container 214(or 248 in FIG. 16) by breaking frangible member 230C where it may bestored prior to transfusion to a recipient. Label 216 (or 249) appliedto storage container 214 (or 248) now carries identifying informationregarding the donor and the fluid. Masked bar codes 224 (or 251)indicate successful treatment of the biological fluid and that noadditional treatment is required. The container may be severed andsealed from the remaining portion of the disposable processing set asgenerally described above.

In addition to the treatment function generally described above and asgenerally depicted in FIG. 22, the control system may prompt theoperator to perform other customer functions at steps 743, 744 and 744a, such as a system settings function at step 745 that allows theoperator to set the date and time at step 748 and select the appropriatelanguage at step 749. The control system also allows the operator toselect certain container management functions such as auto-printing atstep 751, a report printer at step 752, a label printer at step 753 ortransmitting process reports to a data management system at step 754.

Alternatively, the diagnostics menu 755 shown in general in FIG. 23 maybe selected. After waiting for the user to select an option at steps 756and 756 a, the user may select to see product data at step 757, initiatedevice tests at step 758, access service information at step 760 orinitiate diagnostics at step 760. It will be appreciated that steps757-759 may have sub-options like diagnostics step 760. Selectingdiagnostics option 760 permits a maintenance person or supervisor toenter new operator ID information at step 762 to permit new persons tobe authorized to operate light box 10, to over-write bag records at step763, to reset lamp life information, as when lamps are replaced, at step764 and to print a maintenance log at step 765.

It will be appreciated that various modifications of the embodiments andmethods described herein may be made by those skilled in the art withoutdeparting from the scope of the present invention, which is set forth inthe appended claims.

1-14. (canceled)
 15. A method of treating a biological fluid inapparatus with a fluid treatment chamber for receiving and a biologicalfluid, a light source with a plurality of lamps disposed either above orbelow said fluid treatment chamber to treat the biological fluid withlight and a light sensing system with a plurality of light sensors, saidmethod comprising the steps of: sensing the amount of light emitted bysaid plurality of lamps with said plurality of light sensors; developinga plurality of frequency signals from the plurality of light sensors,the frequency of each frequency signal from each of said plurality oflight sensors related to the amount of light received by each lightsensor; providing said plurality of frequency signals to a firstmultiplexer; multiplexing the plurality of frequency signals with saidfirst multiplexer to provide a first multiplexed frequency signal; andcounting the plurality of frequency signals in said first multiplexedfrequency signal with a first counter to provide a first counted outputsignal representative of the amount of light emitted by said pluralityof lamps.
 16. The method of claim 15 comprising the additional step of:providing said plurality of frequency signals from said plurality oflight sensors to a second multiplexer; multiplexing the plurality offrequency signals with said second multiplexer to provide a secondmultiplexed frequency signal; and counting the plurality of frequencysignals in said second multiplexed frequency signal with a secondcounter to provide a second counted output signal also representative ofthe amount of light emitted by said plurality of lamps; and comparingsaid first counted output signal with said second counted output signalto confirm the accuracy of said first second counted output signals. 17.The method of claim 15 comprising the additional step of: providing atleast one test signal of a known frequency to said first multiplexer toenable said light sensing system to assess the counting accuracy of saidfirst counter.
 18. The method of claim 15 comprising the additional stepof: providing a power level input from a power source to said firstmultiplexer to provide information about noise that may be present inthe power system. 19-77. (canceled)
 78. The method of claim 15 whereinsaid light source consists of a plurality of lamps disposed in twoarrays, with one array disposed above said fluid treatment chamber andanother array disposed below said fluid treatment chamber.
 79. Themethod of claim 78 comprising the additional step of: providing saidplurality of frequency signals from said plurality of light sensors to asecond multiplexer; multiplexing the plurality of frequency signals withsaid second multiplexer to provide a second multiplexed frequencysignal; and counting the plurality of frequency signals in said secondmultiplexed frequency signal with a second counter to provide a secondcounted output signal also representative of the amount of light emittedby said plurality of lamps; and comparing said first counted outputsignal with said second counted output signal to confirm the accuracy ofsaid first counted output signals.
 80. The method of claim 78 comprisingthe additional step of: providing at least one test signal of a knownfrequency to said first multiplexer to enable said light sensing systemto assess the counting accuracy of said first counter.
 81. The method ofclaim 78 comprising the additional step of: providing a power levelinput from a power source to said first multiplexer to provideinformation about noise that may be present in the power system.